This research proposal employs fluorescence spectroscopy as a tool to probe the biophysical characteristics of blood cell and brain synaptosomal membranes from patients with Alzheimer's disease. (1) Studies of platelet and RBC membranes may reveal characteristic alterations that may aid in the antemortem diagnosis of Alzheimer's disease. The relationship of observed alterations in blood cell membranes from patients with alzheimer's disease to the demographic and clinical (age at onset, duration, severity, sleep EEG indices) characteristics of this group will be investigated. (2) experiments will also be conducted to determine whether alterations in blood cell membranes from Alzheimer patients reflect a generalized platelet or RBC membrane "defect" or a change in the age-distribution of these cells. In addition to this important clarification, these experiments will provide information on cell membrane changes that accompany the normal aging process of peripheral blood cells. (3) The functional consequence of biophysical abnormalities of platelet membranes will be determined using platelet aggregation as a model system. (4) A parallel study of synaptosomal membranes prepared from fresh, unfixed regions of Alzheimer brain will provide information on membrane biophysical properties as correlated with histopathologic reports. It will, therefore, be possible to determine whether any identified alterations in these synaptosomal membrane properties are more widespread than the characteristic histopathologic abnormalities of Alzheimer's disease and whether the membrane changes are likely to antedate neuronal degeneration and cell loss. To accomplish the proposed research plan, the candidate will obtain additional supervised experience in: (1) blood cell and synaptosomal membrane isolation; (2) the theory and techniques of fluorescence spectroscopy; and (3) the design, execution, and analysis of clinical research studies.